Haematology Department, King's College Hospital NHS Foundation Trust, London, UK.
Hematology Unit, Azienda Ospedaliera Universitaria Sant'Andrea, Rome, Italy.
Invest New Drugs. 2019 Jun;37(3):548-558. doi: 10.1007/s10637-019-00769-5. Epub 2019 Apr 26.
Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naïve, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1 and 2 line respectively. Results from April-2011 to March-2018, 17/51(33%) naïve, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naïve and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naïve respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL.
节拍化疗（M-CHT）在非霍奇金淋巴瘤（NHL）中很少被评估。因此，我们于 2011 年开始在弥漫性大 B 细胞淋巴瘤（DLBCL）患者中尝试一种新的全口服 M-CHT 方案，称为 DEVEC（地塞米松、依托泊苷、长春瑞滨、环磷酰胺、±利妥昔单抗）。方法：我们招募了以下阶段 Ib-IV 的患者：1）初治、虚弱≥65 岁或不适合≥85 岁；2）复发/难治（R/R）≥55 岁。数据从 2011 年 4 月至 2018 年 3 月，前瞻性地从六个意大利中心收集，并与分别在一线和二线接受既定 IV 利妥昔单抗-CHT 治疗的两个参考组的疗效进行比较。结果：17/51（33%）初治、21/51（41%）难治和 13/51（25.5%）复发患者开始接受 DEVEC；51 例患者中 39 例（76.5%）为初发 DLBCL；10 例（19.6%）为转化型 DLBCL 和 2 例（3.9%）为未分类的 DLBCL/经典霍奇金淋巴瘤。中位年龄为 85 岁（范围=77-93），初治和 R/R 分别为 78 岁（范围=57-91），与参考组相比，总体而言，DEVEC 患者的特征非常差。≥3 级血液学不良事件（AE）的发生率为 43%（95%CI=29-58%）：G3 中性粒细胞减少症最常见；≥3 级非血液学 AE 发生率为 13.7%（95%CI=5.4-25.9%），最常见的是感染。初治患者的 1 年 OS 和 PFS 分别为 67%和 61%，参考组初治患者的 OS 和 PFS 分别为 60%和 50%；OS 和 PFS 的 Cox 比例风险比（Cox-PH-ratio）分别为 0.69（95%CI=0.27-1.76；p=.441）和 0.68（95%CI=0.28-1.62；p=.381）。R/R 患者的 1 年 OS 和 PFS 分别为 48%和 39%，参考组 R/R 患者的 1 年 OS 和 PFS 分别为 36%和 17%；OS 和 PFS 的 Cox-PH-ratio 分别为 0.76（95%CI=0.42-1.40；p=.386）和 0.48（95%CI=0.28-0.82；p=.007）。结论：与真实系列相比，DEVEC 的良好疗效和口服给药的便利性，可能为治疗老年 DLBCL 带来范式转变。
